【摘要】 目的研究特异性中性粒细胞弹性蛋白酶抑制剂ＯＮＯ５０４６对移植胰腺再灌注损伤的保护作用。方法应用同系大鼠异位全胰十二指肠移植模型，ＯＮＯ５０４６治疗组的动物移植术前及术后静脉注射ＯＮＯ５０４６，术后定期分批处死受体，测定大鼠血清中性粒细胞化学趋化性细胞因子（ＣＩＮＣ）含量、移植胰腺组织中ＣＩＮＣｍＲＮＡ的表达及髓过氧化酶（ＭＰＯ）活性，并进行组织学观察。结果ＣＩＮＣ于再灌注后３小时出现峰值，治疗组为（７．２４±１．４６）μｇ／Ｌ，对照组为（２８．４±１．８５）μｇ／Ｌ，差异显著；移植物中ＣＩＮＣｍＲＮＡ于再灌注后３小时表达最强，治疗组的表达水平明显低于对照组；ＭＰＯ的活性，治疗组显著低于对照组；治疗组的胰小叶间质水肿及胰小叶间质和胰小叶内的中性粒细胞浸润较轻。结论ＯＮＯ５０４６能抑制ＣＩＮＣ的升高及ＣＩＮＣｍＲＮＡ的表达，抑制中性粒细胞的浸润，对再灌注损伤具有保护作用更多还原

【Abstract】 Objective To study the protective effects of a neutrophil elastase inhibitor(ONO 5046) on reperfusion injury following pancreaticoduodenal transplantation in rats.Methods The homologous male Wistar rat model of heterotopic total pancreaticoduodenal transplantation was used. The ONO 5046 treated animals received the intravenous injection of ONO 5046 5 min before and after operation at a dose of 10mg/kg, and were killed one by one after operation. Serum concentration of cytokine induced neutrophil chemoattractant (CINC) determined by enzyme linked immunosorbant assay, the expression of CINC mRNA detected by Northern blot assay in the pancreatic grafts, and the activity of myeloperoxidase(MPO) were measured. Histological observation was performed.Results The peak of serum CINC concentrations occurred 3h after reperfusion with the difference between the groups with and without ONO 5046 being significant. Expression peak of CINC mRNA in the pancreatic graft occurred 3h after reperfusion with the expression level in the ONO 5046 treated group significantly lower than in the ONO 5046 untreated group. The activity of MPO in the treated group was obviously decreased as compared with in the untreated group. Conclusion ONO 5046 can inhibit the elevation of CINC, the CINC mRNA expression and early neutrophil accumulation in the pancreas, and have protective effects on the ischemia/reperfusion injury of pancreaticoduodenal transplantation.更多还原